@article {318, title = {Artificial Water Channels Enable Fast and Selective Water Permeation Through Water-wire Networks}, journal = {Nature Nanotechnology.}, volume = {15,}, year = {2020}, month = {01/2020}, pages = {73-79}, chapter = {73}, abstract = {

Artificial water channels are synthetic molecules that aim to mimic the structural and functional features of biological water channels (aquaporins). Here we report on a cluster-forming organic nanoarchitecture, peptide-appended hybrid[4]arene (PAH[4]), as a new class of artificial water channels. Fluorescence experiments and simulations demonstrated that PAH[4]s can form, through lateral diffusion, clusters in lipid membranes that provide synergistic membrane-spanning paths for rapid and selective water permeation through water-wire networks. Quantitative transport studies revealed that PAH[4]s can transport \>109\ water molecules per second per molecule, which is comparable to aquaporin water channels. The performance of these channels exceeds the upper bound limit of current desalination membranes by a factor of ~104, as illustrated by the water/NaCl permeability{\textendash}selectivity trade-off curve. PAH[4]{\textquoteright}s unique properties of a high water/solute permselectivity via cooperative water-wire formation could usher in an alternative design paradigm for permeable membrane materials in separations, energy production, and barrier applications.

}, doi = {https://doi.org/10.1038/s41565-019-0586-8}, author = {Woochul Song and Himanshu Joshi and Ratul Chowdhury and Joseph S. Najem and Yue-xiao Shen and Chao Lang and Codey B. Henderson and Yu-Ming Tu and Megan Farell and Megan E. Pitz and Costas D. Maranas and Paul S. Cremer and Robert J. Hickey and Stephen A. Sarles and Jun-li Hou and Aleksei Aksimentiev and Manish Kumar} } @article {308, title = {Atoms to Phenotypes: Molecular Design Principles of Cellular Energy Metabolism}, journal = {Cell}, volume = {179}, year = {2019}, month = {11/2019}, pages = {1098 - 1111.e23}, abstract = {

We report a 100-million atom-scale model of an entire cell organelle, a photosynthetic chromatophore vesicle from a purple bacterium, that reveals the cascade of energy conversion steps culminating in the generation of ATP from sunlight. Molecular dynamics simulations of this vesicle elucidate how the integral membrane complexes influence local curvature to tune photoexcitation of pigments. Brownian dynamics of small molecules within the chromatophore probe the mechanisms of directional charge transport under various pH and salinity conditions. Reproducing phenotypic properties from atomistic details, a kinetic model evinces that low-light adaptations of the bacterium emerge as a spontaneous outcome of optimizing the balance between the chromatophore{\textquoteright}s structural integrity and robust energy conversion. Parallels are drawn with the more universal\ mitochondrial bioenergetic machinery, from whence molecular-scale insights into the mechanism of cellular aging are inferred. Together, our integrative method and spectroscopic experiments pave the way to first-principles modeling of whole living cells.

}, keywords = {bioenergetics, biological membranes, charge transport, chromatophore, integrative model, MD, mitochondria, Molecular Dynamics Simulation, optical spectroscopy, photosynthesis}, issn = {0092-8674}, doi = {10.1016/j.cell.2019.10.021}, url = {http://www.sciencedirect.com/science/article/pii/S0092867419311717}, author = {Abhishek Singharoy and Christopher Maffeo and Karelia H. Delgado-Magnero and David J.K. Swainsbury and Melih Sener and Ulrich Kleinekath{\"o}fer and John W. Vant and Jonathan Nguyen and Andrew Hitchcock and Barry Isralewitz and Ivan Teo and Danielle E. Chandler and John E. Stone and James C. Phillips and Taras V. Pogorelov and M. Ilaria Mallus and Christophe Chipot and Zaida Luthey-Schulten and D. Peter Tieleman and C. Neil Hunter and Emad Tajkhorshid and Aleksei Aksimentiev and Klaus Schulten} } @article {219, title = {The acetylation landscape of the H4 histone tail: disentangling the interplay between the specific and cumulative effects}, journal = {J Am Chem Soc}, volume = {137}, year = {2015}, pages = {6245{\textendash}6253}, doi = {10.1021/jacs.5b00235}, author = {Winogradoff, David and Echeverria, Ignacia and Potoyan, Davit A and Papoian, Garegin A} } @article {13, title = {Assessing graphene nanopores for sequencing DNA.}, journal = {Nano Letters}, volume = {12}, year = {2012}, month = {2012 Aug 8}, pages = {4117-4123}, abstract = {

Using all-atom molecular dynamics and atomic-resolution Brownian dynamics, we simulate the translocation of single-stranded DNA through graphene nanopores and characterize the ionic current blockades produced by DNA nucleotides. We find that transport of single DNA strands through graphene nanopores may occur in single nucleotide steps. For certain pore geometries, hydrophobic interactions with the graphene membrane lead to a dramatic reduction in the conformational fluctuations of the nucleotides in the nanopores. Furthermore, we show that ionic current blockades produced by different DNA nucleotides are, in general, indicative of the nucleotide type, but very sensitive to the orientation of the nucleotides in the nanopore. Taken together, our simulations suggest that strand sequencing of DNA by measuring the ionic current blockades in graphene nanopores may be possible, given that the conformation of DNA nucleotides in the nanopore can be controlled through precise engineering of the nanopore surface.

}, keywords = {DNA, Graphite, Nanopores, Sequence Analysis, DNA}, issn = {1530-6992}, doi = {10.1021/nl301655d}, author = {David B Wells and Maxim Belkin and Jeffrey Comer and Aleksei Aksimentiev} } @article {33, title = {Atoms-to-microns model for small solute transport through sticky nanochannels}, journal = {Lab Chip}, volume = {11}, year = {2011}, month = {2011 Nov 21}, pages = {3766-73}, abstract = {

Modeling the transport of solutes through fluidic systems that have adsorbing surfaces is challenging due to the range of length and time scales involved. The components of such systems typically have dimensions from hundreds of nanometres to microns, whereas adsorption of solutes is sensitive to the atomic-scale structure of the solutes and surfaces. Here, we describe an atomic-resolution Brownian dynamics method for modeling the transport of solutes through sticky nanofluidic channels. Our method can fully recreate the results of all-atom molecular dynamics simulations at a fraction of the computational cost of the latter, which makes simulations of micron-size channels at a millisecond time scale possible without losing information about the atomic-scale features of the system. We demonstrate the capability of our method by simulating the rise and fall of solute concentration in sub-micron-long sticky nanochannels, showing that the atomic-scale features of the channels{\textquoteright} surfaces have a dramatic effect on the kinetics of solute transport in and out of the channels. We expect our method to find applications in design and optimization of micro and nanofluidic systems for solute-specific transport and to complement existing approaches to modeling lab-on-a-chip devices by providing atomic scale information at a low computational cost.

}, keywords = {Microfluidic Analytical Techniques, Molecular Conformation, Molecular Dynamics Simulation, Motion, Nanotechnology, Reproducibility of Results, Surface Properties}, issn = {1473-0189}, doi = {10.1039/c1lc20697d}, author = {Carr, Rogan and Jeffrey Comer and Ginsberg, Mark D and Aleksei Aksimentiev} } @article {49, title = {Analyzing the forces binding a restriction endonuclease to DNA using a synthetic nanopore}, journal = {Nucleic Acids Res}, volume = {37}, year = {2009}, month = {2009 Jul}, pages = {4170-9}, abstract = {

Restriction endonucleases are used prevalently in recombinant DNA technology because they bind so stably to a specific target sequence and, in the presence of cofactors, cleave double-helical DNA specifically at a target sequence at a high rate. Using synthetic nanopores along with molecular dynamics (MD), we have analyzed with atomic resolution how a prototypical restriction endonuclease, EcoRI, binds to the DNA target sequence--GAATTC--in the absence of a Mg(2+) ion cofactor. We have previously shown that there is a voltage threshold for permeation of DNA bound to restriction enzymes through a nanopore that is associated with a nanonewton force required to rupture the complex. By introducing mutations in the DNA, we now show that this threshold depends on the recognition sequence and scales linearly with the dissociation energy, independent of the pore geometry. To predict the effect of mutation in a base pair on the free energy of dissociation, MD is used to qualitatively rank the stability of bonds in the EcoRI-DNA complex. We find that the second base in the target sequence exhibits the strongest binding to the protein, followed by the third and first bases, with even the flanking sequence affecting the binding, corroborating our experiments.

}, keywords = {Computer Simulation, Deoxyribonuclease EcoRI, DNA, DNA-Binding Proteins, Models, Molecular, Nanostructures, Protein Binding}, issn = {1362-4962}, doi = {10.1093/nar/gkp317}, author = {Dorvel, B and G Sigalov and Zhao, Q and Jeffrey Comer and Valentin Dimitrov and Mirsaidov, U and Aleksei Aksimentiev and Gregory Timp} } @article {182, title = {Application of the Euler characteristic to the study of homopolymer blends and copolymer melts}, journal = {Polimery}, volume = {46}, year = {2001}, pages = {309{\textendash}322}, abstract = {

The Euler characteristic is applied to study the phase separation/ordering phenomena occurring in polymer mixtures. Several methods used to compute Euler characteristics are described and discussed in terms of accuracy and efficiency. A novel, robust and exact algorithm based on simplex decomposition is presented. The simulated morphology of spinodal decomposition and the phase equilibrium diagram of gradient copolymers are analyzed in terms of Euler characteristics. Again, the Euler characteristics are applied to specify the connectivity of bicontinuous patterns, to distinguish the disperse and the bicontinuous morphologies, and to detect the percolarion transition. During the spinodal decomposition, the dynamic transformation between the bicontinuous and the droplet patterns is shown to involve the formation of a transient "cylindrical" morphology.

}, url = {http://en.www.ichp.pl/Application-of-the-Euler-characteristic}, author = {Aleksei Aksimentiev and Robert Ho{\l}yst} }